The Imaging Core will provide centralized microanatomical and imaging resources and services for Buck Institute investigators and colleagues at other institutions. The microanatomical resources available include basic histology (tissue fixation and processing, embedding, and morphological stains), immunohistochemistry and immunocytochemistry (immunoperoxidase or alkaline phosphatase procedures with chromagen development), immunofluorescence, and confocal microscopy with Huygen's deconvolution processing and Bitplane Imaris 3D rendering work. The purpose of this proposal is to expand and extend the Core to incorporate a functional imaging facility, enabling investigators to monitor real-time changes in cell function in their models of aging and aging-related disease processes. A wide range of new projects is planned, ranging from those involving the whole nematode to protein interactions within the nucleus. At the center of this expanded capability is a state-of-the-art confocal Zeiss LSM 510 META microscope equipped for functional imaging. The major request in this component is for a full-time Imaging Core research associate, to be fully trained by the Core Director, Dr. David Nicholls, to assist in the planning, execution and processing of functional imaging with this microscope. Additional requests are for service contracts for the microscope and Ti-sapphire pulsed 2-photon laser and a tissue-culture holding facility adjacent to the microscope. In this way this expensive and complex apparatus can be fully utilized by Buck Institute investigators, and also serve as a regional and national resource for research on aging and age-related diseases .